Dosage compensation is a regulatory process that controls the expression of genes related by their linkage to the same sex chromosome. This process is necessary in organisms whose sex-determination mechanisms result in differences between the male (usually XO, XX, or XY) and the female (usually XX) dose of X chromosomes. Dosage compensation equalizes expression of most X-linked genes despite the two-fold difference in X chromosomes, thereby preventing sex-specific lethality resulting from inappropriate amounts of X-chromosome products.
Methods of dosage compensation differ in various species, but all result in the regulation of gene expression along the entire X chromosome. Mammalian dosage compensation consists of random inactivation of one of the two female XX chromosomes which reduces the X chromosome dose to that of the XY male. In C. elegans the transcription level of each X chromosome of the XX hermaphrodite is reduced to achieve the same level as the XO male transcription levels, whereas in Drosophila, the X chromosome of XY males is transcribed at twice the rate as the two X chromosomes in the female.
Two groups of genes are required for activation of dosage compensation in C. elegans; sdc, which is required for both sex determination and dosage compensation, and dpy, which affect only dosage compensation. The DPY-30 nuclear protein is required for the sex-specific localization of the DPY-27-dependent protein complex, which consists of both sdc and dpy gene products, to the hermaphroditic XX chromosomes. The binding of the DPY-27-dependent protein complex to the X chromosomes results in a 50% reduction of X transcript levels.
Loss of DPY-30 function is lethal in XX animals, and results in morphological and behavior abnormalities in XO animals. DPY-30, unlike the other dpy gene products, is not specifically associated with the X chromosome and is expressed independently of the gene hierarchy that controls dosage compensation. Genetic analysis demonstrates that DPY-30 is necessary in early embryogenesis and in developmental processes other than dosage compensation. In XO animals DPY-30 is required for normal mating behavior, normal tail morphology, correct body size, and coordinated movement. It is expressed in moderate levels throughout development in both XX and XO embryos and adults (Hsu, D. et al (1995) Development 121:3323-3334; Hsu, D. and Meyer, B. (1994) Genetics 137:999-1018; Kuroda, M. (1996) Science 274:1633).
The discovery of proteins related to C. elegans DPY-30, and the polynucleotides encoding them, satisfies a need in the art by providing new compositions useful in diagnosis and treatment of disorders associated with cancer and cell growth, development, and proliferation.